Flake-Austin modification of the STA-Peg arthroereisis: a retrospective study.

The Smith subtalar arthroereisis implant (STA-peg) is used to correct severe collapsing pes valgoplanus in children. Flake and Austin modified the placement of this implant to block the leading wall of the lateral talus. Twenty-one patients with a total of 40 STA-peg procedures were evaluated subjectively and objectively. The average age at the time of surgery was 9.7 years (4 to 16 years). The follow-up period averaged 36 months (12 to 90 months). The subjective, objective, and radiographic results were positive and the complication rate was low. A significant advantage of the Flake-Austin modification of the STA-peg placement in transverse planar dominant foot types is also noted.

Intra-pinna anti-tumor vaccination with self-replicating infectious RNA or with DNA encoding a model tumor antigen and a cytokine.

To optimize polynucleotide vaccinations for protective antitumor immunity we used a self-replicating RNA vaccine in which Semliki Forest virus replicase drives RNA expression of the lacZ gene coding for beta-galactosidase as model tumor-associated antigen (TAA). This was compared with replicase-deficient control RNA and with lacZ DNA plasmids with respect to gene expression in vitro and in vivo and for vaccination using the mouse ear pinna as an optimal immunization site. In vitro, the highest expression was observed with self-replicating RNA. Gene expression following pinna inoculation of either non-replicating DNA plasmids or self-replicating RNA was similar, lasting for 2-3 weeks. Higher antibody responses were obtained with RNA than with DNA. beta-Gal peptide specific CTL memory responses to lacZ DNA or RNA lasted for more than 6 weeks while respective responses induced by lacZ-transfected tumor cells lasted for only 2 weeks. To achieve a protective response against lacZ tumor cells with self-replicating RNA about a 100-fold lower dose of polynucleotide was sufficient in comparison to DNA. The extent of protective antitumor immunity not only depended on the gene dose used for vaccination, but also on the aggressiveness of the lacZ-transfected tumor line used for challenge. In comparison to lacZ-transfected tumor cells as vaccines, polynucleotide vaccination also demonstrated superiority with regard to cross-protection. Protective antitumor immunity could be strongly increased upon co-inoculation of lacZ DNA with IL-2 DNA or IL-12 RNA. IL-2 DNA, but not IL-12 RNA, also augmented the CTL response while IL-12 RNA, but not IL-2 DNA, reduced the antibody response. These results demonstrate efficient protective antitumor immunity after intra-pinna lacZ TAA polynucleotide vaccination and show additional immunomodulatory effects by co-administration of cytokine polynucleotides.

Superiority of the ear pinna over muscle tissue as site for DNA vaccination.

Three different vaccination sites were compared for efficiency of immunization with naked DNA. Using the bacterial lacZ gene as a model, all three sites of the mouse (skeletal muscle, dermis of abdominal skin or of the ear pinna) could express the gene product beta-gal but varied in expression time with muscle tissue showing the longest expression. Expression time, however, did not correlate with immune response intensity. The ear pinna was by far the most effective and muscle the least effective priming site for specific humoral and cytotoxic T cell-mediated immune responses. Following intra-pinna DNA inoculation, beta-gal expressing cells were detectable around the injection site and in the major draining lymph node. Efficiency of immunization was also dependent on the promoter and expression vector used. The cytomegalus virus promoter driven pCMV beta vector was superior to the Moloney murine leukemia virus LTR driven BAG vector. LacZ DNA immunization was also compared with cell-based vaccination with lacZ-transfected tumor cells, in which case again the pinna was the best site for inducing strong immune responses. Tumor-specific T cell responses could also be well induced in the pinna, leading to cytotoxic T lymphocyte induction and protective antitumor immunity. Thus, the pinna was found to be a privileged site for induction of antitumor responses and for genetic immunization, an important finding of immediate practical and potential future clinical implications.

Antiviral prophylaxis and the Epstein Barr virus-related post-transplant lymphoproliferative disorder.

Epstein Barr virus (EBV) infection has been associated with the post-transplant lymphoproliferative disorder (PTLD) in up to 8% of transplant recipients. Primary EBV infection and the use of antilymphocyte preparations appear to increase the incidence of PTLD. Experimental evidence suggests that the antiviral prophylaxis used by many transplant programs may influence the development of this post-transplant complication. In order to investigate the influence of antiviral prophylaxis (intravenous ganciclovir followed by high-dose oral acyclovir) on the development of PTLD in kidney-pancreas and liver allograft recipients from the University of Washington Medical Center, records were reviewed for pretransplant EBV status, antilymphocyte preparation use and for histologic documentation of PTLD. Two of 83 kidney-pancreas recipients (1 EBV-seronegative, 1 EBV-seropositive) and 1 of 123 liver recipients (EBV-seropositive) has developed PTLD. Six of 83 kidney-pancreas patients were EBV-seronegative prior to transplantation and 4 of these patients received at least two courses of an antilymphocyte preparation. Thirty-eight (49%) of the 77 EBV-seropositive kidney-pancreas recipients received at least two courses of an antilymphocyte globulin without the development of PTLD. Both the EBV-seronegative kidney-pancreas and the liver recipient who developed PTLD had received multiple courses of antilymphocyte globulins. One EBV-seropositive kidney-pancreas recipient had only received one course of OKT3 1 year prior to the development of PTLD. The incidence of PTLD reported here in patients receiving intravenous ganciclovir followed by high-dose oral acyclovir antiviral prophylaxis is lower than previously recorded when consideration is given for patient's EBV status and the use of antilymphocyte preparations.